DESCRIPTION (Applicant's Abstract): The contribution of edema toward brain swelling and intracranial pressure (ICP) rise, particularly in the case of traumatic brain injury, remains a critical problem. In head injured patients, raised ICP subsequent to uncontrollable brain swelling is the single most frequent cause of death. The goal of this research is to understand the processes by which this swelling, identified by an increase in brain tissue water, is formed and resolved in brain injury. The increased tissue water can be either in the brain extracellular space, intracellular space or a combination of both. Our recent studies have cast a new light on the swelling process and it is our hypothesis that the vasogenic form of edema secondary to blood brain barrier compromise has been overemphasized. It is critical that the type of edema be identified and in an experimental model of traumatic brain injury (TBI) that can produce diffuse swelling and raised ICP. Using these appropriate models, we will utilize new magnetic resonance techniques to discern non-invasively and continuously the type of edema that is developing in the injured brain. We plan to use these models in combination with diffusion weighted imaging techniques and magnetic resonance spectroscopy coupled with gravimetric, electron microscopic, immunocytochemical, and radioactive tracer methods; to test hypotheses related to the type of edema, the contribution of blood volume, the metabolic status, and the changes in barrier permeability that occur with trauma and secondary insult. Acute neurologic assessment and behavioral measures will be correlated with levels of cellular edema in brain injury coupled with secondary insult. Finally, we will apply these methods to determine the efficacy of osmotic diuretics and pressor therapy under conditions where the type of brain swelling has been identified to more clearly discern their utility in ICP management.